"This is the first time a satiation hormone has been linked to these three common diseases in women," said lead author Olle Melander from Skane University Hospital in Malmo, Sweden, in a press statement. "It therefore opens up a new field for continued research on risk assessment and preventive treatment."

In a study of 4632 participants from the Malmo Diet and Cancer Study, fasting levels of the neurotensin precursor proneurotensin were significantly associated with the development of diabetes, CVD, total mortality, CV mortality, and breast cancer in women, over a median follow up period of 13.2-15.7 years (depending on the disease).

As reported in JAMA, a baseline examination conducted in 1991 through 1994 showed that women had significantly higher levels of proneurotensin than men, at a median of 109 versus 99 pmol/L.

In women alone, each standard deviation (SD) increase in proneurotensin was associated with a significantly increased risk for new-onset diabetes, CVD, and all-cause mortality, at hazard ratios (HRs) of 1.41, 1.33, and 1.13, respectively, after adjustment for potential confounders. By contrast, no such significant relationships were observed among men.

Further analysis revealed that there was no significant interaction between gender and proneurotensin levels regarding risk for new-onset diabetes or all-cause mortality.

However, there was a significant interaction between female gender and incidence of CVD.

Furthermore, the excess risk for all-cause mortality among women was mainly accounted for by CV death, with each SD increase in proneurotensin level associated with a 1.5-fold increased risk for CV death.

The team also found that baseline proneurotensin was significantly associated with breast cancer incidence.

"Neurotensin regulates both satiety and breast cancer growth in the experimental setting," say Melander and team "but little is known about its role in the development of breast cancer or cardiometabolic disease in humans."

However, it has been repeatedly shown that estradial upregulates the expression of neurotensin, they note.

"Thus, it can be speculated that the higher proneurotensin observed in women than in men, and the fact that the association between proneurotensin and adverse outcomes was only significant in women, is partially explained by higher lifetime exposure to estrogen in women than in men."

The researchers say their results warrant replication in other prospective population-based studies.

In addition, they suggest that further research should investigate whether targeting the neurotensin system may assist in preventing the diseases in animal models and ultimately in humans.

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